Deciphering the Lipid-Random Copolymer Interactions and Encoding Their Properties to Design a Hybrid System

Abstract

Lipid/copolymer colloidal systems are deemed hybrid materials with unique properties and functionalities. Their hybrid nature leads to complex interfacial phenomena, which have not been fully encoded yet, navigating their properties. Moving toward in-depth knowledge of such systems, a comprehensive investigation of them is imperative. In the present study, hybrid lipid/copolymer structures were fabricated and examined by a gamut of techniques, including dynamic light scattering, fluorescence spectroscopy, cryogenic transmission electron microscopy, microcalorimetry, and high-resolution ultrasound spectroscopy. The biomaterials that were mixed for this purpose at different ratios were 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine and four different linear, statistical (random) amphiphilic copolymers, consisting of oligo(ethylene glycol) methyl ether methacrylate as the hydrophilic comonomer and lauryl methacrylate as the hydrophobic one. The colloidal dispersions were studied for lipid/copolymer interactions regarding their physicochemical, morphological, and biophysical behavior. Their membrane properties and interactions with serum proteins were also studied. The aforementioned techniques confirmed the hybrid nature of the systems and the location of the copolymer in the structure. More importantly, the random architecture of the copolymers, the hydrophobic-to-hydrophilic balance of the nanoplatforms, and the lipid-to-polymer ratio are highlighted as the main design-influencing factors. Elucidating the lipid/copolymer interactions would contribute to the translation of hybrid nanoparticle performance and, thus, their rational design for multiple applications, including drug delivery.

Figure 1

Chemical structure of the utilized biomaterials: (a) DSPC and (b) linear random copolymer P(OEGMA-co-LMA).

Figure 2

Physicochemical characteristics: (a) hydrodynamic radius (R_h, nm) and (b) intensity (kilocounts per second, or kcps) of different hybrid systems in water for injection dispersion medium and at ambient temperature. The standard deviation (SD) in both diagrams is less than 10%. *DSPC:4 hybrid system has a very high R_h compared to the rest of the systems that exceeds the scale of the graph.

Figure 3

Hydrodynamic radius (R_h, nm) of hybrid systems in different dispersion media at 37 °C. The standard deviation (SD) is less than 10%.

Figure 4

GP values derived from Laurdan fluorescence spectra vs % copolymer of DSPC hybrid nanostructures. The standard deviation (SD) is less than 10%.

Figure 5

Cryo-TEM images of DSPC:P(OEGMA-co-LMA) hybrid systems of the different comonomer ratio (varying % PLMA) and/or different oligoethylene glycol side chain length (OEGMA₉₅₀ or OEGMA₅₀₀): (I) DSPC:copolymer-1 in different lipid to polymer weight ratios: a. 9:1, b. 7:3, and c. 5:5 ratio, (II) DSPC:copolymer-2, (III) DSPC:copolymer-3, and (IV) DSPC:copolymer-4. The colored arrows point out a different morphology; namely small spherical particles (red arrow), spherical, or irregular shape particles with distinct membranes (green arrow), rods (yellow arrow), nearly pentagonal-shaped particles (blue arrow), and spherical or irregular-shaped vesicles (black arrow).

Figure 6

mDSC traces of different DSPC/P(OEGMA-co-LMA) hybrid systems.

Figure 7

Results derived from HR-US: Sound speed and b. Attenuation vs temperature for different DSPC/P(OEGMA-co-LMA) hybrid systems.